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Background The main objective of this study to evaluate the association between CPK-MB, CPK, LDH levels and ECG changes to find out the prognosis in patients of organophosphorous poisoning. Methods This was a prospective observational hospital-based study conducted among 94 adult patients who were admitted with history of organophosphorous compound poisoning to the Department of Toxicology in Rajiv Gandhi Government General Hospital, Chennai, after obtaining clearance from Institutional Ethics Committee and written informed consent from the study participants. Results The comparison of initial ECG abnormalities and mean CPK, mean CK-MB, mean LDH values showed a positive correlation with statistical significance. The CPK values & CK-MB values at the time of initial evaluation were found to be significantly higher among the deceased patients in comparison to those discharged. Also, a study on the initial LDH value of deceased patients revealed significantly higher levels as compared to those that of the discharged patients. Conclusion Mortality was observed only in patients whose on admission ECG had QTc prolongation, conduction block, QRS changes, VT and VF. It was observed that the CPK, CK-MB, LDH levels recorded were frequently higher among the OPC poisoning patients. The CPK, CPKMB and LDH values recorded at the time of admission exhibited significantly higher values in the case of the deceased than that of the discharged. On admission, CPK, CK-MB, LDH levels were significantly higher in patients with abnormal ECG as compared to normal ECG. Within each ECG parameter, significant difference was observed in CPK, CK-MB, LDH levels among survived and expired patients. [ABSTRACT FROM AUTHOR]

Background: Poisoning with organophosphorous substances is the commonest cause of inpatient mortality among all poisonings in developing countries like India. This study is undertaken with an aim of assessing simple parameters like GCS and QTc (marker of ventricular arrythmias) in predicting the outcome and complications of organophosphate compound poisoning considering the mortality and sufferings of Organophosphorous poisoning patients. Aim: To assess the utility of GCS score and QTc interval in predicting prognosis in patients who had consumed organophosphate and carbamate poisoning and to assess whether the above parameters helps to identify the high risk groups requiring mechanical ventilation. Materials and methods: This study was conducted among 200 organophosphate and carbamate poisoning patients who were admitted at Government Rajaji Hospital, Madurai from February 2014 to September 2014. After taking detailed history and physical examination and investigations the Glasgow coma scale score and QTc interval at the time of admission was calculated. Patients with GCS score < 13 and QTc interval > 0.44s in males and 0.46s in females as poor outcome. Results: There was a linear relation with QTc interval and severity of Organophosphorous poisoning i.e. as the QTc interval increases the severity of poisoning increases. There was an inverse relationship between the GCS score and severity of Poisoning, .i.e. as the GCS decreases the severity of poisoning increases. Conclusion: Our study showed that respiratory failure in patients with OP compound poisoning can be predicted at admission by simple parameters like lower GCS and prolonged QTc interval in ECG. [ABSTRACT FROM AUTHOR]

Context: Increased use of organophosphate insecticides (OPI) and possibility of terror groups using stocks of nerve agents underscore the need to develop effective and safe antidotes. While intramuscular administration of antidotes like atropine sulphate (AS) has certain lacunae, intravenous route may not be always feasible in emergency field conditions. Objective: Objective was (a) to develop a novel inhalable submicronic-AS respiratory fluid as potential antidote for OPI poisoning, (b)in-vitroandin-vivoevaluation in terms of respiratory fraction, and (c) clinical study to assess drug bioavailability in blood and atropinization pattern post-inhalation. Methods: Formulation was optimized on the basis of particle size of aerosolized droplets andin-vitronebulization rate. Anderson cascade impaction (ACI) studies were carried out to validate the advantage of test formulation in terms of respirable fraction. Six healthy volunteers were inhaled the test formulation and blood bioavailability and atropinization were noted serially. Gamma scintigraphy was used to quantify total and regional lung deposition of nebulized ASin-vivo. Results: The formulation was optimized using 30% ethanol–saline with particle size in the range of 350–500 nm.In-vitroACI data showed high respirable fraction (82.6 ± 3.1%) for the test formulation.In-vivoscintigraphy suggested whole lung deposition of 80.2 ± 6.8% of the total inhaled dose. Early blood bioavailability and atropinization pattern confirmed that therapeutic concentration of the drug in blood was reached within 5 min. Conclusions: 3% submicronic-AS respiratory fluid might be used as potential prophylactic/therapeutic option against OPI poisoning with several advantages over intramuscular injection, including early blood bioavailability and atropinization. [ABSTRACT FROM AUTHOR]

We hypothesized that Tabun poisoning, as well as other organophosphorous treatment, cause specific organs’ oxidative changes that have not previously been substantiated investigated. In this regard, a marker for nitrosative-oxidative stress in the main haemodynamic organs (heart and kidney) could reveal the existence of such changes. In this study, for the first time we studied the nitrosative/oxidative stress in heart and kidney after acute Tabun (Ethyl N,N- Dimethylphosphoramidocyanidate) poisoning measuring by immunohistochemistry the expression of 3-nitrotyrosine—a marker for nitrosative-oxidative stress. We investigated nitrotyrozine expression in three different groups of animals (with at least 3 animals in each group): the first group was treated with 0.5 LD50 Tabun and organs were collected after 24 h; the second group received vehicle for the same period; in the third group a highly specific re-activator was applied immediately after Tabun application. Heart and kidney were collected after 24 h. The levels of nitrotyrozine production significantly increased (more than 3 times) in cardiomyocytes after Tabun. The application of re-activator slightly reduced these levels not reaching the basal heart levels. Nitrotyrozine expression in kidney increased more than 2 times after Tabun and application of re-activator did not change it significantly. In conclusion, our study evidently demonstrated that Tabun trigger oxidative-nitrosative stress in heart and kidney and these cellular effects should be protected by an additional anti-oxidant therapy, since acetylcholinesterase re-activator is not efficient in this manner. [ABSTRACT FROM AUTHOR]

Background: Organophosphorus poisoning (OPP) is a major global public health problem. Pralidoxime has been used in a complimentary role to atropine for the management of OPP. World Health Organization (WHO) recommends use of pralidoxime but studies regarding its role have been inconclusive, ranging from being ineffective to harmful or beneficial. Materials and Methods: The present study was undertaken to evaluate the effectiveness of pralidoxime. Eddleston’s study was the most compelling factor for our study, as he showed worst outcomes using pralidoxime. Our practice of continuous use of pralidoxime was based on the WHO guidelines and the study by Pawar (2006), which showed better outcome with higher doses of pralidoxime. These conflicting results suggested that a re-evaluation of its use in our clinical practice was indicated. Results: There was no difference in mortality rates, hemodynamic parameters and atropine requirements between the AP and A groups. Mean duration of ventilation (3.6 ± 4.6 in AP group vs. 3.6 ± 4.4 in A group) and Intensive Care Unit stay (7.1 ± 5.4 in AP group vs. 6.8 ± 4.7 in A group) was comparable. Serum sodium concentrations showed a correlation with mortality, with lower concentrations associated with better outcomes. Conclusion: The study suggests that add-on WHO-recommended pralidoxime therapy does not provide any benefit over atropine monotherapy. Adding pralidoxime does not seem to be beneficial and at the same time does not result in increased mortality rates. Our practice changed after completion of this study, and it has proven to be of significant benefit to patients who had to bear the expense of treatment. [ABSTRACT FROM AUTHOR]

Introduction: The increased use of organophosphate (OP) insecticides and the ever increasing possibility of terror groups using nerve agents underscore the need to develop effective and safe antidotes against OP poisoning. While intramuscular administration of nerve gas antidotes like atropine sulphate has certain lacunae, intravenous route is neither practical nor feasible in the field conditions for mass casualties. The objective was to develop a novel atropine sulphate nasal drop formulation, evaluate and characterize it using scintigraphy and to carry out safety–efficacy study in human volunteers with a view to obtain early pharmacological effects in comparison to the existing options, particularly the conventional intramuscular route. Methods: Permeability studies were done using atropine sulphate solution containing variable amount of chitosan. Radiometric method was developed for scintigraphy studies while standard spectroscopy was used for the quantification of atropine sulphate in fluids. Concentration of atropine sulphate in nasal drops to produce therapeutic concentration in blood was calculated. Six volunteers (age range 18–53 years) were administered the formulation delivering 6mg of atropine sulphate each. Bioavailability and atropinization were noted serially. Results: Based on the results of in vitro, human scintigraphy and analytical data, 1% atropine sulphate–0.5% chitosan was chosen as the final nasal formulation. Human bioavailability curve was created which showed that the therapeutic concentration of the drug in blood was reached within 5min with nasal drops suggesting that drug delivery through the nasal route is significantly better than the intramuscular route. Unpaired t-test between the means of baseline value of heart rate and that of each time interval showed that increase in heart rate of all the volunteers became significant at 15min (P <0.01) and extremely significant at 30min (P <0.001). Correlation was evident from 5min (c >0.7). Pupil diameter showed maximal increase at 30min (P <0.01). Conclusions: This novel product, 1% atropine sulphate–0.5% chitosan nasal drops might be a safe and efficacious emergency treatment of organophosphorous poisoning with several advantages over the present management, including early atropinization and capability of mass treatment in least amount of time. [Copyright &y& Elsevier]

There is a wide variation and lack of evidence in current recommendations for atropine dosing schedules leading to subsequent variation in clinical practice. Therefore, we sought to examine the safety and effectiveness of a titrated vs. ad hoc atropine treatment regimen in a cohort of patients with acute cholinesterase inhibitor pesticide poisoning. A prospective cohort study was conducted in three district secondary referral hospitals in Sri Lanka using a structured data collection form that collected details of clinical symptoms and outcomes of cholinesterase inhibitor pesticide poisoning, atropine doses, and signs of atropinization. We compared two hospitals that used a titrated dosing protocol based on a structured monitoring sheet for atropine infusion with another hospital using an ad hoc regime. During the study, 272 symptomatic patients with anticholinesterase poisoning requiring atropine were admitted to the three hospitals. Outcomes of death and ventilation were analyzed for all patients, 226 patients were prospectively assessed for atropine toxicity. At baseline, patients in the titrated dose cohort had clinical signs consistent with greater toxicity. This in part may be due to ingestion of more toxic organophosphates. They received less pralidoxime and atropine, and were less likely to develop features of atro- pine toxicity, such as delirium (1% vs. 17%), hallucinations (1% vs. 35%), or either (1% vs. 35%) and need for patient restraint (3% vs. 48%) compared with the ad hoc dose regime. After adjusting for the pesticides ingested, there was no difference in mortality and ventilatory rates between protocols. Ad hoc high dose atropine regimens are associated with more frequent atropine toxicity without any obvious improvement in patient outcome compared with doses titrated to clinical effect. Atropine doses should be titrated against response and toxicity. Further education and the use of a structured monitoring sheet may assist in more appropriate atropine use in anti-cholinesterase pesticide poisoning. [ABSTRACT FROM AUTHOR]

We have described here a new variant of life-threatening organophosphate toxicity syndrome, which produces a brief vocal cord paralysis. A 18 years old male patient with recent ingestion of unknown quantity of Organophosphorous poison, presented to our hospital with acute symptoms of profuse sweating, increased salivation and lacrimation for the first 12 hours. Later on he developed quadriparesis-lower motor neuron (LMN) type - Acute polyneuropathy-myelinopathy. He developed hoarseness of voice and regurgitation of fluids with both 9 and 10 cranial nerve palsies. The patient had developed acute Organophosphorous poison toxicity initially, followed by Intermediate Syndrome after 24 hours of ingestion with vocal cord palsy. [ABSTRACT FROM AUTHOR]

A 32-year-old male presented with a history of consuming some organophosphorous com pound with suicidal intention. He was treated with atropine, pralidoxime, ventilator support. During stay patient had persistent irritability, tachycardiaand hypertension despite sedation and labetalol infusion. He developed headache, visual blurring hemiparesis and focal seizures. Magnetic resonance imaging of the brain revealed multifocal hyperintensities mainly in subcortical areas of parietal and occipital regions in T2-weighted images, with increased values of Apparent Diffusion Coefficient, suggesting posterior reversible encephalopathy syndrome (PRES). The possibilities of PRES caused by organophosphorous poisoning either due to hypertension caused by autonomic deregulation or direct neurological toxicity has been discussed. [ABSTRACT FROM AUTHOR]